title: Active immunization against GnRH reduces the synthesis of GnRH in male rats.
abstract: We sought to determine the effects of active anti-GnRH immunization on GnRH synthesis in the hypothalamus. Adult male rats (n = 36) were randomly and equally allocated into three groups: Control (no treatment), surgically castrated, or immunized against 50 μg D-Lys6-GnRH-tandem-dimer peptide conjugated to ovalbumin in Specol adjuvant at 12 week of age (with a booster 8 week later). Blood samples (for antibody titers and hormone concentrations) were collected at 2-week intervals until rats were killed (20 week). Compared with intact controls, immunocastration reduced (P < 0.05) serum concentrations of testosterone, LH, and FSH, and GnRH content in the median eminence, reduced the weight of the hypohysis (P < 0.01), and induced testicular atrophy (suppression of spermatogenesis). Furthermore, mRNA expression of GnRH in the hypothalamus, GnRH receptor, LH-β and FSH-β in the pituitary, LH receptor and FSH receptor in the testes, and genes in sex steroid feedback loops (androgen receptor [AR], kisspeptin encoded gene (Kiss-1), and kisspeptin receptor (GPR54) in the hypothalamus were decreased in immunocastrated rats compared with intact controls (P < 0.05). Similarly, surgical castration reduced GnRH in the median eminence as well as mRNA expression of GnRH, AR, Kiss-1, and GPR54 in the hypothalamus (P < 0.05). We concluded that anti-GnRH immunization in adult rats reduced synthesis of hypothalamic GnRH by decreasing androgen-AR-Kisspeptin-GPR54 signaling pathways, and caused dysfunction of the pituitary-testicular axis, thereby suppressing spermatogenesis, resulting in testicular atrophy.
authors.affiliation: Isotope Research Lab, Sichuan Agricultural University, Ya'an 625014, People's Republic of China.
authors.forename: Xing-fa
authors.initials: XF
authors.lastname: Han
authors.forename: Xiao-han
authors.initials: XH
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Tang
authors.forename: Xiao-gang
authors.initials: XG
authors.lastname: Du
authors.forename: Xian-yin
authors.initials: XY
authors.lastname: Zeng
mesh_terms: D000818:Animals; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size; D010902:Pituitary Gland / Q000033:anatomy & histology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats / Q000276:immunology*; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000033:anatomy & histology; D013739:Testosterone / Q000097:blood; D014611:Vaccination / Q000662:veterinary*
chemical_list: D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: Anti-GnRH immunization; GnRH; GnRH synthesis; Rat; Reproductive axis